Throughout life, descending activity from the brain shapes spinal cord reflexes to support effective motor function. When injury or disease impairs this long-term supraspinal control, reflex patterns are distorted and spasticity and other disabling problems appear. Better understanding of the mechanisms of supraspinal control of spinal cord plasticity would elucidate the acquisition of motor skills and should lead to novel methods for inducing and guiding recovery of function after injury or disease. Operant conditioning of the spinal stretch reflex (or tendon jerk) or its electrical analog, the H-reflex, is a simple model for exploring long-term supraspinal control of spinal cord plasticity. In response to an operant conditioning protocol, monkeys, rats, mice, and humans can gradually increase or decrease the SSR or the H- reflex. This learning changes the spinal cord, since evidence of it remains even after all supraspinal control is removed. This research project is defining how supraspinal control creates and maintains the spinal cord plasticity underlying H-reflex conditioning, and is learning how reflex conditioning can be used to help restore function after spinal cord injury. The work of the past grant period suggests: that sensorimotor cortex (SMC) and its corticospinal tract (CST) output induce the spinal cord plasticity directly responsible for H-reflex change;that cerebellar output to SMC is essential;and that H-reflex conditioning affects locomotion and can improve it after spinal cord injury. Based on these results and recent pilot data, the hypotheses of this continuation proposal are: (1) that the critical CST activity is produced in the hindlimb area of sensorimotor cortex (SMC) and is guided by the cerebellum;and (2) that reflex conditioning can improve locomotion after a spinal cord contusion injury. The first hypothesis will be tested in rats that undergo down- or up-conditioning of the H-reflex and in control rats. SMC activity and related evoked potentials will be recorded by electrocorticography. The effects of cerebellar and other lesions on this SMC activity will be determined and correlated with the lesion effects on H-reflex conditioning. The second hypothesis will betestedbystudyinglocomotorEMGandkinematicsinrats with calibrated spinal cord contusion injuries before, during, and after up- or down-conditioning of the soleus H-reflex or other spinal reflexes. The locomotor abnormalities produced by spinal cord contusions will be quantified and the impact of spinal reflex conditioning protocols on these abnormalities will be determined. The results should yield new understanding of how the brain shapes spinal cord reflexes so that they support effective motor function. They should lead to novel methods that use reflex conditioning to induce and guide spinal cord plasticity so as to improve function after spinal cord injury or other trauma or disease. Reflex conditioning protocols could be designed to target the particular deficits of each individual, and could thereby complement more general therapeutic methods (e.g., locomotor training) to help maximize restoration of function.

Public Health Relevance

The brain continually changes spinal cord reflexes throughout life. These reflex changes support normal motor skills and also contribute to the functional deficits associated with neuromuscular disorders. This project is revealing the mechanisms of these reflex changes, and showing how they can be induced and guided to increase recovery of function after spinal cord injury or with other injury or disease.